Abstract 3144: Mitochondrial Rnas Regulate Endothelial Function Through Nuclear Transcription

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 44; no. Suppl_1
• Main Authors: Sriram, Kiran, Yuan, Dongqiang, Malhi, Naseeb, Tapia, Alonso, Luo, Yingjun, Liu, Xuejing, Zhen, Chen
• Format: Journal Article
• Language: English
• Published: 01.05.2024
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/atvb.44.suppl_1.3144

Abstract only Mitochondrial-nuclear communication is vital for cellular homeostasis and response to environmental stress. The known messengers for mitochondria to communicate their functional status to the nucleus include ATP, ROS, and Ca 2+ . It remains unclear whether the immediate output of mitochondrial transcription, i.e., the mitochondrial RNAs (mtRNAs), are a type of messenger to communicate to the nucleus. Herein, we show that mt RNAs are attached to the nuclear genome and thus constitute a subset of the c hromatin- a ssociated RNA (mt-caRNA). Mt-caRNAs preferentially attach to promoter regions and the attachment levels change in response to cellular stress, i.e. high glucose and TNFα (HT). We identify the mitochondrial non-coding RNA SncmtRNA as a mt-caRNA. In human endothelial cells (ECs), suppression of SncmtRNA attenuates HT stress induction of nascent RNA transcribed from the nuclear genome, including the cell adhesion molecules ICAM1 and VCAM1, and abolishes stress-induced monocyte-EC adhesion. In addition to SncmtRNA, we show nuclear localization of other mtRNAs such as mt-CYB and mt-ND5, which is increased in the diabetic human condition. Collectively, our findings suggest the potential involvement of many mtRNAs in mitochondrial-nuclear communications and that mt-caRNAs may regulate nuclear transcription and thus play a role in mediating cellular response in health and disease.